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Study in Circulation provides detail on how low blood flow promotes vascular disease
Date:6/23/2008

Researchers have found the first direct proof that a key protein drives the clogging of arteries in two ways, and that lowering levels of it opens them up, according to study results published in the June edition of the journal Circulation. The work establishes cyclophilin A as an exciting target in the design of drugs against atherosclerosis, the number one cause of heart attacks and strokes, which occur when vessels become completely blocked. While the study was in mice, higher levels of the study protein have also been found in the blood of human patients with diseased blood vessels.

The current results build on three major discoveries in cardiovascular science in the last 20 years. The first is that fast blood flow, as it moves along the straight portions of blood vessel walls, creates frictional force that protects those areas against atherosclerosis. At the points where one vessel branches into two, however, blood flow is slowed, frictional force lessened and atherosclerotic plaques more likely to form. Among the consequences of low flow is the creation of highly reactive molecules called reactive oxygen species, which oxidize molecules they encounter and impair vascular function.

The second discovery was that the reaction of the body's immune system to fatty build-up in arteries is as great a contributor to heart attack risk as the fatty build-up itself. Vessel walls mistake fatty deposits for intruders, akin to bacteria, and call in white blood cells to prevent infection. The same cells, unfortunately, also cause inflammation that contributes to clogs and generate more reactive oxygen species.

In the third discovery, researchers realized that blood vessels to do not just stand by as fatty deposits build up, but instead fight to stay open by aggressively growing (remodeling). Once they reach their growth limit however, the same growth that kept vessels open for so long begins contributing to the clogs by thickening ves
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Contact: Greg Williams
Greg_Williams@urmc.rochester.edu
585-273-1757
University of Rochester Medical Center
Source:Eurekalert

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